Following vesicle fusion the neurotransmitter molecules are released and diffuse across the synaptic cleft (a very rapid process) and bind to receptors on the postsynaptic membrane. This binding leads to the opening (or less often the closing) of ion channels. These channels are termed ligand-gated because their opening and closing are primarily controlled by the binding of neurotransmitter. This mechanism can be contrasted with that of the voltage-gated channels underlying the action potential, whose opening and closing are determined by the membrane potential. However, there are some channels, most notably the NMDA (N-methyl-Daspartate) channel, that are both ligand and voltage gated.
It is also worth noting here that what follows in this section refers to what happens when neurotransmitter binds to receptors in which the ion channel is part of the receptor itself. These receptors are referred to as ionotropic receptors and underlie what is now called “fast” synaptic transmission. There is also “slow” synaptic transmission, mediated by what are called metabotropic receptors, in which the receptor and ion channel are not part of the same molecule, and binding of neurotransmitter to the receptor initiates biochemical cascades that lead to postsynaptic potentials with slow onsets (see the section Receptors for details). Despite the differing time courses, many of the same basic principles apply to both types of postsynaptic potential.
EPSPs. As stated earlier, the binding of neurotransmitter generally changes the membrane potential of the postsynaptic cell, and these changes are referred to as EPSPs when they increase the excitability of the neuron and IPSPs when they inhibit the neuron from firing action potentials. EPSPs are always depolarizing potentials, and IPSPs are usually hyperpolarizing.
Once a ligand-gated channel is open, the direction of current flow through it is determined by the electrochemical driving force for the permeant ion(s). It turns out that the pores of most channels that underlie EPSPs are relatively large and therefore allow passage of most cations with similar ease. As an example, consider the acetylcholinegated channel that is opened at the neuromuscular junction. Na+ and K+ are the major cations present (Na+ extracellularly and K+ intracellularly); therefore, the net current through the channel is approximately the sum of the Na+ and K+ currents (Inet = INa + IK). Recall that the current through a channel from a particular ion is dependent on two factors: the conductance of the channel to the ion and the driving force on the ion. This relationship is expressed by the equation
Equation 6.1 where gx is the conductance of the channel to ion x, Vm is the membrane potential, and Ex is the Nernst equilibrium potential for ion x. In this case gx is similar for Na+ and K+ , so the main determinant of net current is the relative driving forces (Vm − Ex). If the membrane is at its resting potential (typically around −70 mV), there is a strong driving force (Vm − ENa) for Na+ to enter the cell because this potential is far from the Na+ Nernst potential (about +55 mV), whereas there is only a small driving force for K+ to leave the cell because Vm is close to the K+ Nernst potential (about −90 mV). Thus, if acetylcholine-gated channels open when the membrane is at its resting potential, a large inward Na+ current and a small outward K+ current will flow through the acetylcholine channel, thereby resulting in a net inward current, which acts to depolarize the membrane.
The net inward current that results from opening such channels is called the excitatory postsynaptic current (EPSC).